The invention relates to the use of autoantibodies for tumor therapy and prophylaxis.
Neoplasia is often caused by somatic mutations. When these mutations accumulate with age, the burden on the immune system, which controls neoplasia as one of its functions, is increased. However, despite increased cancer-related mortality rates in the aged, many aged individuals do not develop tumors. One explanation for this immunity is that certain natural antibodies play a role in humoral anti-tumor immunity (Chow et al., Int. J. Cancer, 27: 459-469, 1981). However, little is known about the antigenic specificity of such antibodies.
One type of natural antibody found in the immune system is the autoantibody. These autoantibodies have been repeatedly found in significantly higher titers in older humans and laboratory animals without overt disease than in younger controls (Whitaker, et al., Clin. Res., 14: 143, 1966; Cammarata, et al., JAMA, 199: 115-118, 1967; Siegel, et al., Immunology, 22: 457-463, 1972). Hybridomas that produce natural autoantibodies from mice of different ages have been described (Sakharova, et al., Zh. Obshch. Biol., 47: 625-630, 1986).
The occurrence of autoantibodies in the aged is believed to serve as a marker of a disregulated immune system, and these antibodies recently have been prescribed with tumor growth-enhancing properties (Ben-Yehuda, et al., Cancer Invest., 10: 525-531, 1992). In earlier studies, others have noted that elevated levels of serum autoantibodies can result in the development of autoimmune systemic diseases (Dixon, et al., Progress in Immunology, 959-995, New York: Academic Press, 1980), and that antinuclear autoantibody suppression by the immunosuppressive drug cyclophosphamide may correlate with growth of a proliferating lymphoreticular neoplasm (Walker, et al., Clin. Exp. Immunol., 24: 210-217, 1976). Hahn et al., Arthrit. Rheumat., 18: 145-152 (1975), concluded that cyclophosphamide enhanced production of neoplasms such as lymphoreticular neoplasms, carcinomas, and sarcomas.